Family 2.A.57 - The Equilibrative Nucleoside Transporter Family       

Family ID: 52640

Several members of the ENT family have been functionally characterized (Griffiths et al., 1997; Sundaram et al., 1998; Vasudevan et al., 1998; M?ser et al., 1999). The hENT1 is of human placental origin, is 456 amino acyl residues long and possesses eleven putative a-helical transmembrane spanners (TMSs). It is expressed in many human tissues. Homologues have been sequenced from yeast, protozoa, nematodes and mammals. C. elegans possesses at least five such homologues. Among these are the two smaller nucleolar "delayed early response" gene products, HNP36, sequenced from humans and mice (Williams and Lanahan, 1995). The hENT1 and rENT1 proteins appear to exhibit broad specificity for purine and pyrimidine nucleosides and cytotoxic nucleoside analogues used in cancer and viral chemotherapy. Some are sensitive and others are insensitive to inhibition by nitrobenzyl thioinosine. hENT2 has higher affinity for adenosine, inosine and hypoxanthine than hENT1 but lower affinity for other nucleosides. Both human and rat isoforms are cell surface and organellar localized being found in mitochondria, nuclear envelopes and lysosomes.

Two nucleoside transporters were initially identified in Trypanosoma brucei and in Leishmania donovani, respectively. Both transport adenosine and probably other nucleosides and nucleobases as well as several drugs. When reconstituted in yeast, the former transporter (called TbAT1) catalyzes adenosine uptake and confers susceptibility to melaminophenyl arsenicals. Tyrpanocide drug-resistant tyrpanosomes have a mutated TbAT1 gene. These protozoan proteins are 460-500 residues long and exhibit 10 putative TMSs. A second inosine/guanosine transporter has recently been identified.